Research is proposed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes involving 20 of the 24 different chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes will be mapped that code for some 60 enzymes, as well as plasma membrane proteins, ribosomal proteins, and viral characteristics. The enzymes are associated with inherited diseases incluing hemolytic anemias and neurodegenerative disorders, the lysosome, essential metabolic pathways, and aspects of development. The plasma membrane proteins, ribosomal proteins, lysomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetics disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.